(4R)-4-benzyl-2-(3H-imidazol-4-ylmethyl)-5-thiophen-2-ylsulfonyl-2,5-diazabicyclo[5.4.0]undeca-8,10,12-triene-9-carbonitrile

Base Information

• Chemical Name: (4R)-4-benzyl-2-(3H-imidazol-4-ylmethyl)-5-thiophen-2-ylsulfonyl-2,5-diazabicyclo[5.4.0]undeca-8,10,12-triene-9-carbonitrile
• CAS No.: 195987-41-8
• Molecular Formula: C₂₅H₂₃N₅O₂S₂
• Molecular Weight: 489.622
• Mol file: 195987-41-8.mol

Synonyms:1H-1,4-Benzodiazepine-7-carbonitrile,2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-,(3R)- (9CI); 1H-1,4-Benzodiazepine-7-carbonitrile,2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-,(R)-; (R)-2,3,4,5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine-7-carbonitrile;BMS 214662

Chemical Property of (4R)-4-benzyl-2-(3H-imidazol-4-ylmethyl)-5-thiophen-2-ylsulfonyl-2,5-diazabicyclo[5.4.0]undeca-8,10,12-triene-9-carbonitrile

Chemical Property:

• Vapor Pressure: 5.38E-25mmHg at 25°C
• Boiling Point: 790.9°Cat760mmHg
• PKA: 13.19±0.10(Predicted)
• Flash Point: 432.1°C
• PSA: 129.71000
• Density: 1.45g/cm³
• LogP: 5.24898

Purity/Quality:

97% ^*data from raw suppliers

BMS214662 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: BMS 214662 is a potent inhibitor of farnesyltransferase (FTase; IC50 = 1.3 nM). It is selective for FTase over geranylgeranyl transferase (GGTase; IC50 = 1,900 nM). It inhibits the growth of MEK2, A2780, and PC3 cancer cells expressing wild-type Ras (IC50s = 2.5, 0.04, and 0.15 μM, respectively), as well as HCT116, MIP, RC-165, and MIA PaCa-2 cells expressing mutant K-Ras (IC50s = 0.06, 0.3, 0.3, and 0.12 μM, respectively). BMS 214662 induces apoptosis in HCT116 cells in a concentration-dependent manner. In vivo, BMS 214662 (600 mg/kg) is curative in an HCT116 mouse xenograft model. It also reduces tumor growth in Calu-1, HT-29, EJ-1, and MIA PaCa-2 mouse xenograft models.
• Uses: A potent and selective inhibitor of farnesyltransferase that induces mitochondrial apoptosis in chronic myeloid leukemia stem/progenitor cells, including CD34+38- cells, through activation of protein kinase Cβ.

Technology Process of (4R)-4-benzyl-2-(3H-imidazol-4-ylmethyl)-5-thiophen-2-ylsulfonyl-2,5-diazabicyclo[5.4.0]undeca-8,10,12-triene-9-carbonitrile

There total 17 articles about (4R)-4-benzyl-2-(3H-imidazol-4-ylmethyl)-5-thiophen-2-ylsulfonyl-2,5-diazabicyclo[5.4.0]undeca-8,10,12-triene-9-carbonitrile which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 93.0%

5-imidazolecarboxaldehyde (3034-50-2) + (R)-2,3,4,5-tetrahydro-3-(phenylmethyl)-4-(thien-2-ylsulfonyl)-1H-1,4-benzodiazepine-7-carbonitrile (195985-38-7) → BMS-214662 (195987-41-8)

Guidance literature:

With triethylsilane; trifluoroacetic acid; In dichloromethane; at 20 ℃; for 4h;

DOI:10.1016/S0040-4039(00)02257-7

Reference yield: 80.0%

C31H29N5O5S3 → BMS-214662 (195987-41-8)

Guidance literature:

With potassium t-amylate; In tetrahydrofuran;

DOI:10.1021/acs.oprd.8b00307

Reference yield:

(R)-7-bromo-2,3,4,5-tetrahydro-3-(phenylmethyl)-1H-1,4-benzodiazepine (195984-33-9) → BMS-214662 (195987-41-8)

Guidance literature:

Multi-step reaction with 3 steps

1.1: 80 percent / 1-methyl-2-pyrrolidinone / 3.5 h / 200 °C

2.1: 7.8 g / DIEA / CH₂Cl₂ / 58 h / 20 °C

3.1: AcOH / 1,2-dichloro-ethane / 1 h / 60 °C

3.2: 35 percent / NaBH(OAc)3 / 1,2-dichloro-ethane

With 1-methyl-pyrrolidin-2-one; acetic acid; N-ethyl-N,N-diisopropylamine; In dichloromethane; 1,2-dichloro-ethane; 1.1: Substitution / 2.1: Sulfonylation / 3.1: Condensation / 3.2: Reduction;

DOI:10.1021/jm000248z

upstream raw materials:

5-imidazolecarboxaldehyde

(R)-2,3,4,5-tetrahydro-3-(phenylmethyl)-4-(thien-2-ylsulfonyl)-1H-1,4-benzodiazepine-7-carbonitrile

(R)-7-bromo-2,3,4,5-tetrahydro-3-(phenylmethyl)-1H-1,4-benzodiazepine

(R)-2,3,4,5-tetrahydro-3-(phenylmethyl)-1H-1,4-benzodiazepine-7-carbonitrile

Refernces

• 1、 Shi, Zhongping,Fan, Junying,Kronenthal, David R.,Mudryk, Boguslaw M.. "Development of a Practical Synthesis of a Farnesyltransferase Inhibitor". . p. 1534 - 1540. Retrieved 2018/11/23.